Nouscom’s Off-the-Shelf Neoantigen Immunotherapy, NOUS-209, Continues to Elicit Potent and Durable Immune Responses in Lynch Syndrome Carriers Highlighting its Potential to ‘Intercept’ Cancer

• Lynch Syndrome (LS) is a common hereditary condition (affecting one in 300) conferring a high risk of developing colorectal, gastric, endometrial and other cancers
• NOUS-209 monotherapy is well tolerated and generates potent and long-lasting neoantigen-specific T cell responses

• Updated data to be presented at the Society for Immunotherapy of Cancer (SITC) 2024 Annual Meeting

BASEL, Switzerland – 5^th November 2024 - Nouscom, a clinical stage immuno-oncology company developing off-the-shelf and personalized neoantigen cancer immunotherapies, announces further promising data from the fully enrolled Phase 1b/2 study evaluating NOUS-209 for its potential to ‘intercept’ cancer in Lynch Syndrome (LS) carriers.

These updated data demonstrate that NOUS-209 monotherapy induces potent, broad and durable immune responses in all LS carriers evaluated and continues to be well-tolerated with no treatment-related serious adverse events reported. The new data will be presented at the Society for Immunotherapy of Cancer (SITC) Annual Meeting in Houston, TX, USA on Saturday 9^th November 2024.

NOUS-209 is an off-the-shelf immunotherapy encoding 209 neoantigens that are shared across both sporadic and hereditary deficient Mismatch Repair (dMMR) / Microsatellite Instable (MSI) tumors. LS carriers have a high-risk, genetic predisposition to developing MSI tumors such as colorectal cancer (CRC) and other types of life-threatening cancers, including endometrial, gastric and ovarian. Once diagnosed, people with LS undergo intensive and invasive surveillance programs that may include pre-emptive surgery but otherwise have no approved treatment options available.

In the ongoing Phase 1b/2 trial evaluating NOUS-209 as a monotherapy (NCT05078866), immune responses were evaluated in 23 LS carriers. NOUS-209 monotherapy continued to be safe, well tolerated and to generate potent immunogenic CD4 and CD8 T cell responses in all 23 participants. T cell responses were shown to be potent, broad and durable against multiple neoantigens encoded within NOUS-209. These data continue to support future clinical development of NOUS-209 as a valuable intervention for intercepting cancer in LS carriers.

Final data from the Phase 1b/2 study are expected to be available in mid-2025 and discussions with regulators regarding the future clinical development of NOUS-209 in LS carriers are underway.

The study is led by researchers at The University of Texas MD Anderson Cancer Center, in collaboration with the Cancer Prevention Clinical Trials Network and sponsored by the National Cancer Institute (grant # UG1CA242609).

“Lynch Syndrome affects about one in 300 people, making it one of the most common hereditary cancer syndromes. Vaccine development is a significant step forward for the LS community, which currently relies on routine screening tools for cancer prevention”, said the study’s principal investigator, Eduardo Vilar-Sanchez, M.D., Ph.D., Professor of Clinical Cancer Prevention at MD Anderson. “The updated data further suggest that cancer interception may be possible and that NOUS-209 has the potential to become an important intervention for people with LS, who face an elevated risk of developing life-threatening cancers, such as colorectal, gastric, and endometrial.”

Dr. Elisa Scarselli, Chief Scientific Officer of Nouscom, added: “These exciting data substantially reinforce those first presented in a late-breaking oral abstract presentation at SITC last year¹, and further highlight the ability of NOUS-209 monotherapy to safely and effectively induce long-lasting immune responses in Lynch Syndrome carriers. This strengthens our belief that the immune system can be primed to intercept pre-malignant lesions and prevent the development of MSI tumors. We greatly appreciate the contribution and dedication of our collaborators at the US National Cancer Institute, clinical investigators and LS carriers who participated in this trial, all of whom share our commitment to intercept cancer.”

Dr. Marina Udier, Chief Executive Officer of Nouscom, commented: “The data we are seeing from the Phase 1b/2 trial with NOUS-209 as a monotherapy in Lynch Syndrome carriers are extremely encouraging. Together with the previously published positive Phase 1 data of NOUS-209 in combination with pembrolizumab in dMMR/MSI cancers, and our ongoing randomized Phase 2 trial of NOUS-209, also in combination with pembrolizumab in dMMR/MSI metastatic CRC, NOUS-209 has demonstrated induction of powerful neoantigen-specific immune responses. These responses could lead to clinical benefits and highlight the transformative potential of NOUS-209, from cancer interception to treatment of metastatic disease^2,3.

“Primary data read-outs from both the randomized Phase 2 trial in MSI mCRC and the Phase 1b/2 trial in LS are expected by mid-2025. We are excited to plan the future clinical development for NOUS-209 including a path towards registration.”

Details of the poster presented at SITC 2024 are as follows:

• Title: Nous-209 vaccine induces shared neoantigen immunogenicity for cancer interception in healthy Lynch Syndrome carriers: results from Phase Ib/II trial
• Number: 638
• Date: Saturday, 9^th November 2024
• Session: Clinical Trials in Progress

• Presenter: Dr. Eduardo Vilar-Sanchez, M.D., Ph.D., Professor of Clinical Cancer Prevention at MD Anderson

The abstract can be viewed on SITC’s website here .

Ends

References

1. D’Alise M. et al. Nous-209 genetic vaccine encoding shared cancer neoantigens is safe and elicits robust immune response in healthy Lynch syndrome carriers: interim results from Phase 1 cancer interception trial. Journal for ImmunoTherapy of Cancer (2023);11: doi: 10.1136/jitc-2023-SITC2023.1526
2. D’Alise, M. et al. Adenoviral Based-Vaccine Promotes Neoantigen Specific CD8+ T Cell Stemness And Tumor Rejection, Science Translational Medicine (2022); 14, 657

3. Overman, M. et al. Meeting Abstract 2023 ASCO Annual Meeting Results of phase I-II bridging study for Nous-209, a neoantigen cancer immunotherapy, in combination with pembrolizumab as first line treatment in patients with advanced dMMR/MSI-h colorectal cancer. https://ascopubs.org/doi/pdf/10.1200/JCO.2023.41.16_suppl.e14665

About Lynch Syndrome

Lynch Syndrome (LS) is a common hereditary condition associated with an increased predisposition to develop colorectal cancer (CRC) and other type of cancers, including endometrial, gastric and ovarian. LS carriers have a 50% to 80% and 40% to 60% lifetime risk of developing CRC or endometrial cancer, respectively, with an elevated risk of developing several other tumor types (Bonadona et al. JAMA 2011).

LS is caused by mutations in one of the four DNA mismatch repair (MMR) genes, leading to tumors that accumulate a large number of neoantigens. In the general population, approximately one in 300 individuals have LS (Win et al 2017, Cancer Epidemiol Biomarkers Prev). In the US, it’s estimated that nearly one million individuals are affected by LS. Despite this, LS remains vastly underdiagnosed and current intervention options are limited to invasive surveillance and/ or prophylactic surgery.

Neoantigen-targeted immunotherapy, NOUS-209, is being explored for its potential to stimulate the immune system to recognize and intercept tumors before they occur.

About MSI Tumors

Microsatellite instability (MSI) tumors are a subset of cancers characterized by a high frequency of mutations within short, repetitive DNA sequences known as microsatellites. This instability occurs due to defects in the mismatch repair (MMR) system, which normally corrects errors that arise during DNA replication. When the MMR system is deficient (dMMR), cells accumulate genetic mutations, leading to MSI tumors. MSI is particularly common in colorectal, endometrial, and certain gastric cancers and is associated with Lynch Syndrome.

About Nouscom

Nouscom is a clinical-stage immuno-oncology company developing next-generation, off-the-shelf and personalized cancer immunotherapies. Nouscom’s proprietary viral vector platform has the capacity to encode for large payloads of neoantigens or other immunomodulators and clinically demonstrated to safely and potently harness the power of the immune system.

Nouscom is currently advancing the clinical development of its wholly owned programs:

• NOUS-209, an off-the-shelf neoantigen cancer immunotherapy for the treatment of MSI solid tumors in combination with pembrolizumab in randomized Phase 2 trials.

• NOUS-209, an off-the-shelf monotherapy in Lynch Syndrome carriers with the potential to ‘intercept cancer’ before it advances. A Phase 1b/2 is being conducted under a clinical trial collaboration and supply agreement with the National Cancer Institute (NCI).

• NOUS-PEV, a personalized cancer immunotherapy, is expected to enter randomized Phase 2 trials in indications with high unmet medical need in 2025.

Nouscom has also exclusively out-licensed VAC-85135, an off-the-shelf immunotherapy developed under a multi-project agreement, which is currently under evaluation in a Phase 1 trial for the treatment of Myeloproliferative Neoplasms sponsored by Janssen Research & Development and Bristol Myers Squibb.

For more information on Nouscom, please visit the company’s website at www.nouscom.com or follow us on LinkedIn.

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